Immunomodulatory ultrathin coatings for pancreatic islet transplantation

ID：MPS/dmr/bmat(7623)1306110 PI：Kharlampieva，Eugenia ORG：阿拉巴马大学伯明翰分校题目：免疫调节性超薄多层涂层用于胰岛移植技术：尽管胰岛细胞移植已成为一种有前途的1型糖尿病治疗方法，但由于免疫抑制的不良反应和同种异体移植功能的下降，其临床应用仍受到限制。为了克服这些障碍，提出了一种临床前方法来保护孤立的胰岛和调节1型糖尿病的自身免疫反应。这项建议的目的是开发具有受控免疫调节和炎症反应的新型细胞保护涂层，并深入了解涂层活性的基本机制，以保持胰岛的活性和功能。这些涂层将通过具有抗氧化和抗炎特性的细胞相容大分子的层层氢键组装来设计。本研究的目标如下：(1)采用层层氢键组装的方法合成超薄涂层材料。通过氢键作用，合成了一系列新型的具有抗氧化剂金属卟啉结构的功能共聚物，并进行了自组装。(2)确定无胰岛涂层的体外免疫调节作用。将获得一种具有高级抗氧化和抗炎活性的新型聚合物涂料。这些涂层是可适应的，并且可以进一步修改，以促进非侵入性成像。(3)评价胰岛上涂层对免疫应答的体外免疫调节作用。这些努力将建立与生物材料特性和胰岛功能的基本关联，并为以快速有效的方式修饰其他活细胞类型提供变革性知识。非技术性：拟议的研究为开发用于基础研究的新型细胞保护材料以及糖尿病患者的基于细胞的移植治疗提供了新的机会。我们的建议是特别及时的，因为目前的胰岛包裹系统由于高细胞毒性和大注射量的要求而对移植具有挑战性。新型免疫保护材料的设计将为开发具有独特特性的生物材料开辟新的前景，使其在生物工程、组织工程等生物相关领域得到应用。这个项目的教育目标是在UAB开发一个以发现为导向的、多学科的生物材料/聚合物科学计划，以促进从高中到研究生的多样性。该研究所目前正在UAB开发一个聚合物科学项目，重点是理科和博士级别的生物材料。高中生、本科生和研究生，包括未被充分代表的少数民族，将接受生物聚合物科学的现代方面的培训，包括最先进的合成和分析方法，并将参与UAB内外的密集多学科合作。拟议的活动将促进化学系、外科系和微生物学系之间的跨学科合作研究。这些合作努力将促进UAB生物医学研究界对以聚合物为基础的专门生物材料作为细胞移植治疗新平台的需求的认识。这些成果将通过同行评议期刊上的出版物以及在国家和国际科学会议上的介绍来传播。

ID: MPS/DMR/BMAT(7623) 1306110 PI: Kharlampieva, Eugenia ORG: University of Alabama-BirminghamTitle: Immunomodulatory Ultrathin Multilayer Coatings for Pancreatic Islet TransplantationTechnical: Although transplantation of pancreatic islet cells has emerged as a promising treatment for Type 1 diabetes, its clinical application remains limited due to adverse effects of immunosuppression and declining allograft function. To overcome these hurdles, a preclinical approach to protect isolated islets and to modulate autoimmune responses in Type 1 diabetes is proposed. The goal of this proposal is to develop novel cytoprotective coatings with controlled immunomodulatory and inflammatory responses, and to gain insight into the fundamental mechanism of the coating activity to preserve islet viability and function. These coatings will be designed through layer-by-layer hydrogen-bonded assembly of cytocompatible macromolecules with antioxidant and anti-inflammatory characteristics. The objectives of the proposed study are as follows: (1) Synthesize ultrathin coating materials with a layer-by-layer hydrogen-bonded assembly approach. A series of novel functional copolymers with antioxidant metalloporphyrin modality will be synthesized and self-assembled through hydrogen-bonding interactions. (2) Define the immunomodulatory effects of 'islet-free' coatings in vitro. A novel polymer coating with advanced antioxidant and anti-inflammatory activity will be obtained. The coatings are adaptable and can be further modified to facilitate non-invasive imaging. (3) Evaluate the immunomodulatory effects of 'on-islet' coating in response to immune challenges in vitro. These efforts will establish fundamental correlations with biomaterial properties and islet function, and provide transformative knowledge for modification of other living cell types in a rapid and efficient manner. Non-Technical: The proposed research presents new opportunities for the development of novel cytoprotective materials to be used for basic research applications as well as a cell-based transplantation therapy for diabetic recipients. Our proposal is particularly timely since current islet encapsulation systems are challenging for transplantations due to high cytotoxicity and the requirement for large injection volumes. The design of novel immunoprotective materials will open new prospects for developing biomaterials with unique characteristics having applications in various bio-related areas such as bioengineering and tissue engineering. The educational objective of this project is to develop a discovery-driven, multidisciplinary biomaterials/polymer sciences program at UAB to promote diversity from the high school through graduate-level. The PI is currently developing a polymer science program at UAB with a specific focus on biomaterials at the B.S. and Ph.D. levels. High school, undergraduate, and graduate students, including underrepresented minorities, will be trained in modern aspects of biopolymer science including state-of-the-art synthetic and analytical methods, and will take part in intensive multidisciplinary collaborations throughout and beyond UAB. The proposed activities will develop interdisciplinary collaborative research between the Departments of Chemistry, Surgery, and Microbiology. These collaborative efforts will stimulate awareness of the needs of the UAB biomedical research community for specialized polymer-based biomaterials as novel platforms for cell transplantation therapy. The results will be disseminated through publications in peer-reviewed journals and presentations at national and international scientific conferences.